Sphingosine-1-phosphate reduces hepatic ischaemia/reperfusion-induced acute kidney injury through attenuation of endothelial injury in mice

So Young Lee, Dong Hee Kim, Su Ah Sung, Myung Gyu Kim, Won Yong Cho, Hyoung Kyu Kim, Sang Kyung Jo

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Aim: Hepatic ischaemia/reperfusion injury (IRI) frequently complicates acute kidney injury (AKI) during the perioperative period. This study was to determine whether hepatic IRI causes AKI and the effect of the sphingosine-1-phosphate (S1P) on AKI. Methods: S1P and vehicle were given to mice before ischaemia and mice were subjected to hepatic IRI. Plasma creatinine (PCr), alanine transaminase (ALT), urinary neutrophil gelatinase-associated lipocalin (NGAL) and renal histological changes were determined. As a marker of endothelial injury, vascular permeability was measured. The effect of VPC 23019, a S1P1 receptor antagonist, was also assessed. Results: Hepatic IRI resulted in liver injury (increased ALT) and systemic inflammation. Kidneys showed elevated inflammatory cytokines, leucocyte infiltration, increased vascular permeability, tubular cell apoptosis and increased urinary NGAL, although PCr did not increase. Pretreatment with S1P resulted in an attenuation of systemic inflammation and kidney injury without any effect on plasma ALT or peripheral lymphocytes. The protective effect of S1P was partially reversed by VPC 23019, suggesting the important contribution of the S1P/S1P1 pathway to protect against hepatic IRI-induced AKI. Conclusion: The study data demonstrate the important contribution of systemic inflammation and endothelial injury to AKI following hepatic IRI. Modulation of the S1P/S1P1 receptor pathway might have some therapeutic potential in hepatic IRI-induced kidney injury. Ischaemia/reperfusion-induced liver damage can result in injury to remote organs such as the heart, lungs and kidney. In this paper, a mouse model of partial hepatic ischaemia followed by reperfusion was used to demonstrate the contribution of systemic inflammation and endothelial injury to the development of the associated acute kidney injury.

Original languageEnglish
Pages (from-to)163-173
Number of pages11
JournalNephrology
Volume16
Issue number2
DOIs
Publication statusPublished - 2011 Feb

Keywords

  • acute kidney injury
  • endothelial dysfunction
  • hepatic ischaemia/reperfusion injury
  • sphingosine-1-phosphate

ASJC Scopus subject areas

  • Nephrology

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